Antioxidant and anti-inflammatory action (in vivo and in vitro) from the trunk barks of Cabreúva (Myrocarpus frondosus Allemao, Fabaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Myrocarpus frondosus, known as cabreúva, is a tree whose trunk barks are used in folk medicine as tea, syrup, ointments, and tinctures for the treatment of inflammation. However, there is no scientific evidence demonstrating this activity. AIM OF THE STUDY: The present investigation was focused on evaluating the antioxidant and anti-inflammatory activities of M. frondosus, using the in vitro model of RAW 264.7 macrophages induced by LPS and the in vivo model of mouse pleurisy induced by carrageenan. MATERIALS AND METHODS: M. frondosus trunk barks were dried at room temperature for seven days and subjected to exhaustive maceration with ethanol (70%) to obtain its crude extract (CE). CE was subjected to UPLC-HRMS analysis to establish its chemical profile. Its antioxidant activity was evaluated using the DPPH method, reducing power by the iron (III) to iron (II) reduction assay and the ß-carotene-linoleic acid bleaching assay. The RAW 264.7 macrophages were pretreated with the CE in a non-cytotoxic concentration and induced by LPS (1 µg/mL). After 24 h, using the supernatant, we evaluated the nitric oxide (NOx) and interleukin-6 (IL-6) levels. The anti-inflammatory effects of CE (at doses of 30, 100 and 300 mg/kg) were evaluated on leukocyte migration (total and differential), exudate concentrations, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities, NOx, tumor necrosis factor-α (TNF-α), and IL-6 levels, by using a murine model of neutrophilic inflammation. RESULTS: The UPLC-HRMS of CE revealed the presence of isoflavonones, including biochanin A and formononetin. CE exhibited good antioxidant activity by quenching and decreasing free radicals, as well as reducing pro-oxidant metals. CE did not show cytotoxicity at a concentration below 11 µg/mL and reduced the secretion of the pro-inflammatory NOx in the inflamed macrophages. In vivo assay revealed that CE caused a pronounced inhibition on leukocyte migration, and this inhibition was due to its ability to reduce neutrophil migration. Moreover, CE was also able to reduce the release of critical pro-inflammatory mediators such as MPO, NOx, TNF-α, and IL-6. CONCLUSIONS: All these findings indicate that M. frondosus exhibited antioxidant activity and anti-inflammatory effect.

Phenolic Compounds Isolated from Calea uniflora Less. Promote Anti-Inflammatory and Antioxidant Effects in Mice Neutrophils (Ex Vivo) and in Mice Pleurisy Model (In Vivo).

The literature shows that phenolic compounds possess important antioxidant and anti-inflammatory activities; however, the mechanism underlying these effects is not elucidated yet. The genus Calea is used in folk medicine to treat rheumatism, respiratory diseases, and digestive problems. In this context, some phenolic compounds were isolated with high purity from Calea uniflora Less. and identified as noreugenin (NRG) and α-hydroxy-butein (AH-BU). The aim of this study was to analyze the effect of these compounds on cell viability, the activity of myeloperoxidase (MPO), and apoptosis of mouse neutrophils using ex vivo tests. Furthermore, the effect of these compounds on the cytokines, interleukin 1 beta (IL-1ß), interleukin 17A (IL-17A), and interleukin 10 (IL-10), and oxidative stress was investigated by analyzing lipid peroxidation (the concentration of thiobarbituric acid reactive substances (TBARS)) and activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), using a murine model of neutrophilic inflammation. The NRG and AH-BU reduce MPO activity and increase neutrophil apoptosis (p < 0.05). These compounds reduced the generation of oxygen reactive species and IL-1ß and IL-17A levels but increased IL-10 levels (p < 0.05). This study demonstrated that NRG and AH-BU show a significant anti-inflammatory effect by inhibiting the MPO activity and increasing neutrophil apoptosis in primary cultures of mouse neutrophils. These effects were at least partially associated with blocking reactive species generation, inhibiting IL-1ß and IL-17A, and increasing IL-10 levels.

Phenolic constituents from Wissadula periplocifolia (L.) C. Presl. and anti-inflammatory activity of 7,4'-di-O-methylisoscutellarein.

This study reports the first phenolics from Wissadula genus (Malvaceae) and the anti-inflammatory activity of 7,4'-di-O-methylisoscutellarein. Using chromatographic methods, five phenolic compounds were isolated from aerial parts of Wissadula periplocifolia (L.) C. Presl. The compounds were identified as 4-hydroxybenzoic acid, 3-hydroxybenzoic acid, trans-cinnamic acid, tamgermanetin and 7,4'-di-O-methylisoscutellarein using spectroscopic methods. The flavone 7,4'-di-O-methylisoscutellarein showed anti-inflammatory activity by inhibiting neutrophils recruitment in a mice model of pleurisy and by decreasing significantly the production of cytokines IL-1ß and TNF-α.

Evidence for the involvement of TNF-α and IL-1ß in the antinociceptive and anti-inflammatory activity of Stachys lavandulifolia Vahl. (Lamiaceae) essential oil and (-)-α-bisabolol, its main compound, in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Stachys lavandulifolia Vahl (Lamiaceae) is a medicinal plant widely used in Turkey and Iranian folk medicine due to its analgesic and anti-inflammatory properties, but little is known about its essential oil. AIM OF THIS STUDY: We studied the antinociceptive and anti-inflammatory effects of S. lavandulifolia essential oil (EOSl) and (-)-α-bisabolol (BIS), its main compound, in algogen-induced orofacial nociceptive behavior in mice, and assessed the possible involvement of pro-inflammatory cytokines in these profiles. MATERIALS AND METHODS: The GC-FID and GC-MS analysis of EOSl demonstrated the presence of (-)-α-bisabolol (56.4%), bicyclogermacrene (5.3%), δ-cadinene (4.2%) and spathulenol (2.9%) as the main compounds. Male Swiss mice were pretreated with EOSl (25 or 50mg/kg, p.o.), BIS (25 or 50mg/kg, p.o.), morphine (3mg/kg, i.p.) or vehicle (saline 0.9% with two drops of tween 80, 0.2%), before formalin- (20µl, 2%), capsaicin- (20µl, 2.5µg) or glutamate- (20µl, 25Mm) injection into the right upper lip (perinasal area) in mice. The anti-inflammatory profile of EOSl or BIS (50mg/kg) was assessed by the inflammatory response induced by carrageenan (2% in 0.2mL) in mice (pleurisy model). RESULTS: Our results showed that p.o. treatment with EOSl and BIS displayed significant inhibitory (p<0.05 or p<0.01 or p<0.001) effects in different orofacial pain tests on mice, but BIS proved to be more effective, significantly reducing nociceptive behavior in all tests including both phases of the formalin test. The analgesic effect is not related to any abnormality since EOSl- or BIS-treated mice exhibited no performance alteration in grip strength. Moreover, EOS1 and BIS exhibited a significant anti-inflammatory effect (p<0.001) in the pleurisy model of inflammation, which seems to be related to a significant reduction (p<0.05) of the pro-inflammatory cytokine TNF-α in BIS treatment, and of the pro-inflammatory cytokine IL-1ß (p<0.01) in EOS1 treatment. CONCLUSION: Our results corroborate the use of S. lavandulifolia in traditional medicine as an analgesic and anti-inflammatory, which seems to be related to (-)-α-Bisabolol, the main compound of EOSl.

Anti-hyperalgesic and Anti-inflammatory Activity of Alternanthera Maritima Extract and 2″-O-α-L-rhamnopyranosylvitexin in Mice.

Alternanthera maritima are used in Brazilian popular medicine for the treatment of inflammatory and infectious diseases. Species of Alternanthera have demonstrated biological activities in previous scientific studies. The aim of this study was to determine whether the ethanol extract of the aerial parts of A. maritima (EEAM) and the isolated compound 2″-O-α-L-rhamnopyranosyl-vitexin inhibit mechanical hyperalgesia and parameters of inflammation in mice. The oral administration of EEAM significantly inhibited carrageenan (Cg)-induced paw edema and reduced leukocyte migration into the pleural cavity. 2″-O-α-L-rhamnopyranosylvitexin significantly inhibited paw edema and reduced both leukocyte migration and the leakage of protein into the pleural cavity. Both EEAM and 2″-O-α-L-rhamnopyranosylvitexin significantly prevented the Cg-induced hyperalgesia. Local administration of 2″-O-α-L-rhamnopyranosylvitexin significantly prevented the Cg- and tumor necrosis factor (TNF)-induced hyperalgesia. In conclusion, this study demonstrated that EEAM is an anti-inflammatory and anti-hyperalgesic agent, and the results suggested that 2″-O-α-L-rhamnopyranosylvitexin is responsible for the effects of EEAM and the mechanism involves the TNF pathway.

Antinociceptive and anti-inflammatory activity of the siaresinolic acid, a triterpene isolated from the leaves of Sabicea grisea Cham. & Schltdl. var. grisea.

In the present study, siaresinolic acid (siaresinol, SA) was isolated from the leaves of Sabicea grisea and studied to evaluate its antinociceptive and anti-inflammatory activity. The antinociceptive effect of SA was investigated in mice using different animal models to study pain. In the acetic acid-induced writhing test, intraperitoneal (i.p.) injection of SA (0.1, 1, and 10 mg/kg, i.p.) 1 h before a pain stimulus significantly reduced the nociceptive response (by 42.3, 68.2, and 70.9 %, respectively). Pretreatment with glibenclamide, but not with yohimbine, metoclopramide, ketanserin, or naloxone, restored the antinociceptive effect induced by SA in the writhing test, suggesting that the K(+)ATP channel pathway might be involved in its mechanism of action. In the formalin test, SA (1 mg/kg, i.p.) decreased licking time in the second phase only, thereby indicating an anti-inflammatory effect. In the hot plate test, there was no significant difference in nociceptive behavior. In the rota-rod test, it was verified that a high dose of SA (10 mg/kg, i.p.) did not affect the locomotor activity of mice. In the pleurisy model, induced by carrageenan, treatment with SA inhibited important events involved in inflammatory responses, namely leukocyte influx, plasma leakage, and increased inflammatory mediators (TNF-α, IL-1ß, and chemokine CXCL1), in the pleural exudate. Additionally, SA itself was not cytotoxic when evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in macrophages cultured for 24 h at concentrations ranging from 1 to 200 µg/mL. These results suggest, for the first time, that SA attenuates nociceptive behavior through mechanisms involving receptors for ATP-dependent potassium channels, in addition to suppressing acute inflammatory responses.

Polygala molluginifolia A. St.-Hil. and Moq. prevent inflammation in the mouse pleurisy model by inhibiting NF-κB activation.

UNLABELLED: This study was conducted to investigate the anti-inflammatory activity of Polygala molluginifolia (Polygalaceae) on the mouse pleurisy model induced by carrageenan. P. molluginifolia is a plant native to southern Brazil that is popularly called "canfora". The Polygala genus is used to treat different pathologies, including inflammatory diseases, in traditional medicine. MATERIAL AND METHODS: The whole P. molluginifolia plant material was extracted by maceration with 96% ethanol. The crude hydroalcoholic extract (CE) was subjected to chromatographic procedures to produce various derivate fractions, including its aqueous (Aq), ethyl acetate (EtOAc), and hexane (Hex) fractions. Compound 1 (5,3',4'-trihydroxy-6″,6″-dimethylpyrano [2″,3″:7,6] isoflavone) (Iso), which was isolated from the EtOAc fraction, and Compound 2 (rutin) (Rut), which was isolated from the Aq fraction, were identified using ¹H and ¹³C NMR spectroscopy and quantified using an HPLC apparatus. RESULTS: The CE, the Aq, EtOAc, and Hex fractions, and the isolated compounds Iso and Rut were able to reduce cell migration and exudation. Furthermore, the plant material also decreased the myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities and the nitric oxide (NO(x)), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1ß) levels. In addition, Iso and Rut reduced the TNF-α and IL-1ß mRNA expression levels and significantly decreased NF-κB p65 phosphorylation. CONCLUSION: The results show that P. molluginifolia has a significant anti-inflammatory action and that this effect is due, at least in part, to the presence of Iso and Rut in large amounts. Moreover, this effect was found to be closely related to the inhibitory effects of the isolated compounds on the NF-κB pathway.

Grape seed proanthocyanidin extract protects against carrageenan-induced lung inflammation in mice through reduction of pro-inflammatory markers and chemokine expressions.

Proanthocyanidins are the most abundant phenolic compounds and have been reported to exert anti-inflammatory actions. The aim of this study was to investigate the effects of grape seed proanthocyanidin extract (GSPE) in a mouse model of carrageenan-induced pleurisy. Following the induction of pleurisy using λ-carrageenan (Cg, 1 %), GSPE (25, 50 and 100 mg/kg) was administered per-oral (p.o.), and the glucocorticoid-induced tumour necrosis factor receptor (GITR), IL-17A expressing cells and other markers, such as cytokines (Th1/Th2 and Th17), were studied. We evaluate the effects of GSPE on the mRNA expression of pro-inflammatory and anti-inflammatory mediators. The results illustrated that the cell numbers of IL-17A and GITR expressing cells and the cytokine levels in Th1/Th17 cells were markedly increased in the Cg-group, whereas the cytokines produced by Th2 cells were significantly decreased in the same group. Treatment with GSPE reversed these effects. Histological examinations revealed anti-inflammatory effects of GSPE.

Indicaxanthin from cactus pear fruit exerts anti-inflammatory effects in carrageenin-induced rat pleurisy.

Nutritional research has shifted recently from alleviating nutrient deficiencies to chronic disease prevention. We investigated the activity of indicaxanthin, a bioavailable phytochemical of the betalain class from the edible fruit of Opuntia ficus-indica (L. Miller) in a rat model of acute inflammation. Rat pleurisy was achieved by injection of 0.2 mL of λ-carrageenin in the pleural cavity, and rats were killed 4, 24, and 48 h later; exudates were collected to analyze inflammatory parameters, such as nitric oxide (NO), prostaglandin E(2) (PGE(2)), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α); cells recruited in pleura were analyzed for cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) expression, and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation. Indicaxanthin (0.5, 1, or 2 µmol/kg), given orally before carrageenin, time- and dose-dependently, reduced the exudate volume (up to 70%) and the number of leukocytes recruited in the pleural cavity (up to 95%) at 24 h. Pretreatment with indicaxanthin at 2 µmol/kg inhibited the carrageenin-induced release of PGE(2) (91.4%), NO (67.7%), IL-1ß (53.6%), and TNF-α (71.1%), and caused a decrease of IL-1ß (34.5%), TNF-α (81.6%), iNOS (75.2%), and COX2 (87.7%) mRNA, as well as iNOS (71.9%) and COX-2 (65.9%) protein expression, in the recruited leukocytes. Indicaxanthin inhibited time- and dose- dependently the activation of NF-κB, a key transcription factor in the whole inflammatory cascade. A pharmacokinetic study with a single 2 µmol/kg oral administration showed a maximum 0.22 ± 0.02 µmol/L (n = 15) plasma concentration of indicaxanthin, with a half-life of 1.15 ± 0.11 h. When considering the high bioavailability of indicaxanthin in humans, our findings suggest that this dietary pigment has the potential to improve health and prevent inflammation-based disorders.

Croton antisyphiliticus Mart. attenuates the inflammatory response to carrageenan-induced pleurisy in mice.

The aim of this study was to investigate the anti-inflammatory effect of the crude hydroalcoholic extract (CHE) from the aerial parts of Croton antisyphiliticus, its fractions and isolated compounds derived from it on the mouse model of pleurisy induced by carrageenan. The aerial parts of C. antisyphiliticus were dried, macerated and extracted with ethanol to obtain the CHE, which was fractionated by liquid-liquid extraction using solvents with increasing polarity to obtain hexane (Hex), ethyl acetate (EA) and aqueous (Aq) fractions. Vitexin and quinic acid were isolated from Aq fraction. Capillary electrophoresis analysis, physical characteristics and spectral data produced by infrared (IR), nuclear magnetic resonance ((1)H and (13)C NMR) and mass spectrometry analyses were used to identify and elucidate the structure of the isolated compounds. The experimental model of pleurisy was induced in mice by a single intrapleural injection of carrageenan (1 %). Leukocytes, exudate concentrations, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities and nitrate/nitrite (NOx), tumor necrosis factor-α (TNF-α) and interleukin-17 (IL-17) levels were determined in the pleural fluid leakage at 4 h after pleurisy induction. Animals pre-treated with CHE, Hex, EA, Aq, vitexin and quinic acid exhibited decreases in leukocytes, exudate concentrations, MPO and ADA activities and NOx levels (p < 0.05). Also CHE, Hex, EA and vitexin but not quinic acid inhibited TNF-α and IL-17 levels (p < 0.05). C. antisyphiliticus caused anti-inflammatory effect by inhibiting the activated leukocytes, exudate concentrations, NOx, TNF-α, and IL-17 levels. The compounds vitexin and quinic acid may be responsible for this anti-inflammatory action.

Systemic administration of Rosmarinus officinalis attenuates the inflammatory response induced by carrageenan in the mouse model of pleurisy.

Rosmarinus officinalis, also named rosemary, is a native plant from the Mediterranean region that is useful for the treatment of inflammatory diseases. Studies using experimental models and/or in vitro tests have shown the important biological effects of rosemary. In this context, the mechanism of the anti-inflammatory activity of rosemary must be investigated to support the discovery of new substances with anti-inflammatory effects. The aim of the present study was to investigate the anti-inflammatory effects of crude extract oil free obtained from the leaves of rosemary in an animal model of inflammation, thus evaluating its medicinal use for the treatment of inflammatory conditions. Also its ethanol, hexane, and ethyl acetate fractions, as well as its isolated compounds carnosol and rosmarinic acid were analyzed. Swiss mice were used for the in vivo experiments. The effect of this herb on the inhibition of the leukocytes, exudation, myeloperoxidase, and adenosine-deaminase activities, nitrite/nitrate, interleukin 17A, and interleukin 10 levels and mRNA expression was determined. The crude extract and its derived fractions, in addition to its isolated compounds, inhibited leukocytes and decreased exudation and myeloperoxidase and adenosine-deaminase activities, as well as nitrite/nitrate and interleukin 17A levels and mRNA expression, besides increasing interleukin 10 levels and mRNA expression. Rosemary showed important anti-inflammatory activity by inhibiting leukocytes and decreasing exudation. These effects were associated with a decrease in the proinflammatory parameters (myeloperoxidase, adenosine-deaminase, nitrite/nitrate, and interleukin 17A) and an increase in the anti-inflammatory cytokine (interleukin 10). This study confirms the anti-inflammatory properties of rosemary and validates its use in folk medicine to treat inflammatory diseases such as rheumatism and asthma.

Anti-inflammatory and antioxidant properties of hydroalcoholic crude extract from Casearia sylvestris Sw. (Salicaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris Sw. is widely used in popular medicine to treat inflammatory conditions. AIM OF THE STUDY: To investigate the anti-inflammatory and antioxidant properties of hydroalcoholic crude extract (HCE) taken from Casearia sylvestris Sw. (Salicaceae). METHODS AND RESULTS: The effect of the HCE from this plant (3-300 mg/kg) on the reduction of inflammatory response to carrageenan was investigated in pleurisy in rats (intrapleural, 2% in 0.2 mL) or paw edema in mice (intraplantar, 300 µg/20 µL, right hind paw). The plant anti-inflammatory action was assessed by its capability in inhibiting cell migration, enzymatic activity of myeloperoxidase (MPO) and production of nitrite/nitrate or edema. The in vitro antioxidant activity of this extract against lipid peroxidation and damage to proteins was assessed as possible pathways to contribute as anti-inflammatory mechanisms. Carrageenan-induced hind paw edema (739.3 ± 11.9 µm) was reduced by HCE (30 mg/kg: 462.8 ± 28.38 µm) to similar extents as dexametasone (365.1 ± 16.7). In pleurisy, treatment of the animals with HCE (100mg/kg: 0.010 ± 0.001 mU/mg of protein) also reduced MPO activity augmented by carrageenan (0.020 ± 0.001 mU/mg of protein) as well as leukocytes migration (carrageenan: 17.8890 ± 2.3900 leukocytes/mL, HCE 100mg/kg: 7.0880 ± 9631 leukocytes/mL). Significant effects were also observed in animals treated with different doses of HCE in biochemical tests for oxidative stress analysis. CONCLUSION: The anti-inflammatory and antioxidant effects of HCE from Casearia sylvestris Sw. suggests a potential therapeutic benefit of this plant in treatment of inflammatory conditions.

Anti-inflammatory and antinociceptive activities of LQFM002 - A 4-nerolidylcatechol derivative.

AIMS: The current study describes the synthesis and pharmacological evaluation of (E)-N-(3,7-dimethylocta-2,6-dienyl)-1,3-dimethyl-1H-pyrazol-5-amine (LQFM002), a compound originally designed through a molecular simplification strategy from 4-nerolidylcatechol. LQFM002 was evaluated for preservation of the PLA(2) enzyme inhibitory effects of the lead compound, 4-nerolidylcatechol, using in vitro and in vivo models. MAIN METHODS: Rota-rod, open field and pentobarbital-induced sleeping tests were used to evaluate the effects of LQFM002 on the central nervous system. A gel plate assay of PLA(2) activity, carrageenan-induced pleurisy and TNF-α levels was used to assay anti-inflammatory activity. Antinociceptive activities of LQFM002 were evaluated with acetic acid-induced writhing, formalin and hot-plate tests, while involvement of the opioid pathway in the LQFM002 antinociceptive effect was investigated with naloxone pre-treatment. KEY FINDINGS: LQFM002 inhibited PLA(2) activity, cell migration into the pleural cavity, and capillary permeability (Evan's blue concentration) and reduced TNF-α levels in pleural exudates. LQFM002 also reduced acetic acid-induced writhing and the licking time in both phases of the formalin test and increased latency in the hot-plate test. Pre-treatment with 8.25 µmol/kg naloxone (3mg/kg) reversed the analgesic effects of LQFM002 in the early phase of the formalin test. SIGNIFICANCE: LQFM002 showed anti-inflammatory activity, which possibly involved reduction of leukocyte migration and TNF-α levels. LQFM002 also demonstrated inhibition of PLA(2) activity in vitro. LQFM002 had an antinociceptive effect that involved the opioidergic system.

Relationship of chemical structure and anti-inflammatory activity of dihydrocorynantheol and its analogues.

BACKGROUND: Dihydrocorynantheol (DHC) is an alkaloid compound isolated from Esenbeckia leiocarpa Engl. that has demonstrated anti-inflammatory properties in experimental models. The aim of this study was to investigate whether the modification of the chemical structure of DHC could alter its anti-inflammatory effect in a mouse model of pleurisy induced by carrageenan. METHODS: DHC was isolated from Esenbeckia leiocarpa Engl. Capillary electrophoresis, physical characteristics, spectral data produced by infrared analysis and nuclearmagnetic resonance ((1)H and (13)C), and mass spectrometry analysis were used to identify and elucidate DHC structure. The DHC compound was subjected to chemical structural modifications by nucleophilic substitution reactions, yielding five analogous compounds: acetyl (1), p-methylbenzoyl (2), benzoyl (3), p-methoxybenzoyl (4) and p-chlorobenzoyl (5). Swiss mice were used throughout the experiments. Pro-inflammatory parameters leukocyte migration, exudate concentrations and myeloperoxidase (MPO) activity were quantified in the fluid leakage from the mouse pleural cavities at 4 h after pleurisy induction. RESULTS: DHC and its analogues acetyl, p-methylbenzoyl, benzoyl, p-methoxybenzoyl and p-chlorobenzoyl inhibited total and differential leukocyte migration and MPO activity (p < 0.05). Only DHC significantly decreased the exudate concentrations (p < 0.01). CONCLUSIONS: DHC was more effective than its analogues as an anti-inflammatory agent in the mouse model of pleurisy induced by carrageenan. We did not determine what physicochemical modifications altered the anti-inflammatory effect of DHC, but this effect may be due to the modifications on the hydroxyl group at carbon 17 of the DHC.

From popular use to pharmacological validation: a study of the anti-inflammatory, anti-nociceptive and healing effects of Chenopodium ambrosioides extract.

UNLABELLED: ETHNO-PHARMACOLOGICAL RELEVANCE: Chenopodium ambrosioides (Amarantaceae) is an annual or perennial plant popularly known as 'erva de Santa Maria', 'mastruço' and 'erva-do-formigueiro'. This herb is used in folk medicine in the form of teas, poultices and infusions for inflammatory problems, contusions and lung infections, and as an anthelmintic and anti-fungal. AIM OF THE STUDY: The aim of the present study was to further the understanding of the anti-nociceptive, anti-inflammatory and wound healing effects of ethanol extract (EE) obtained from the leaves and stems of Chenopodium ambrosioides in animal models of acute pain, inflammation and wound healing, thus supporting its medicinal use for the treatment of pain and inflammatory conditions MATERIALS AND METHODS: The anti-nociceptive activity of EE (150-500 mg/kg) was evaluated using the nociception induced by formalin (2.5%), prostaglandin-E(2) (PGE2; 3 nmol/paw), capsaicin (CAP, 1.6 µg/paw) and bradykinin (BK, 10 nmol/paw). The anti-inflammatory activity of EE (150-500 mg/kg) was evaluated in carrageenan- (Cg, 300 µg/paw), PGE(2)- (3 nmol/paw), substance P- (SP, 20 nmol/paw) and BK- (3 nmol/paw) induced paw oedema. The topical anti-inflammatory activity of EE (1%, 3% and 5%) was evaluated in arachidonic acid- (AA, 2mg/ear), oil croton- (1 µg/ear) and CAP- (250 µg/ear) induced ear oedema. The effect of this extract in the inhibition of the influx of neutrophil, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities and nitric oxide (NO) and TNF-á levels was also determined using the mouse of pleurisy induced by Cg. The excision wound model in rats was used to evaluate the wound healing efficacy of EE (1%, 3% and 5%). To exclude the possible non-specific muscle relaxant or sedative effects of EE, mice motor performance was also evaluated with the rota-rod test. RESULTS: EE (5% per ear) was effective in reducing ear oedema induced by croton oil by 78.09%, CAP by 70.85% and AA by 77.02%. EE (500 mg/kg; p.o.) also significantly inhibited paw oedema induced by Cg by 40%, PGE(2) by 51%, SP by 56% and BK by 57%. EE (500 mg/kg; p.o.) inhibited the cell influx of leucocytes by 78% and neutrophils by 53%, MPO activity by 62.22% and ADA activity by 23.07%, as well as NO by 77.77% and TNF-á levels by 50% in the fluid leakage due to the carrageenan-induced pleurisy. EE also inhibited the formalin-induced nociceptive in both phases of pain (neurogenic and inflammatory) at a dose of 500 mg/kg, resulting in inhibitions of 77.39% and 95.60%, respectively. EE (500 mg/kg; p.o.) was also effective in inhibiting the nociception induced by PGE(2) (68%), CAP (53%) and BK (32%). Topical application of EE (5%) on excision wounds caused a significant reduction in wound area when compared with the untreated controls. Finally, treatment with EE (150-500 mg/kg) did not show any significant alterations in motor performance or body temperature compared with the control group. CONCLUSIONS: The results, including the inhibition of mediators (BK, NO, SP, PGE(2) and TNF-á) and enzyme (MPO and ADA) activity, validate the use of the plant under study for therapeutic treatment of anti-inflammatory, painful and wound healing processes.

Inhibitory effect of anethole in nonimmune acute inflammation.

Anethole [1-methoxy-4-(1-propenyl)benzene] occurs naturally as a major component of the essential oil of star anise (Illicium verum Hook.f., family Illiciaceae), comprising more than 90 % of its volatile components. Studies showed that this substance has antioxidant, antibacterial, antifungal, and anesthetic properties. In this study, the anti-inflammatory properties of anethole in animal models of nonimmune acute inflammation such as croton oil-induced ear edema and carrageenan-induced pleurisy were investigated. The investigated parameters were edema formation, leukocyte migration, and inflammatory mediators involved. Oral administration of anethole at a dose of 250 and 500 mg/kg reduced both the volume of pleural exudates and the number of migrated leukocytes. Levels of nitric oxide (NO) and prostaglandins (PGE2) in the inflammatory exudate were reduced by treatment with anethole, but levels of tumor necrosis factor-α and interleukin-1ß were not significantly altered. In ear edema, the oral treatment with anethole inhibited the formation of exudate and the activity of myeloperoxidase, but not after topical administration. These results suggest that the anethole may be effective in controlling some nonimmune acute inflammation-related disease, probably by an inhibitory action on production and/or release of PGE2 and NO.

The novel Sinupret® dry extract exhibits anti-inflammatory effectiveness in vivo.

Sinupret® is frequently used as a herbal medicinal product to treat sinusitis, and it was assumed that anti-inflammatory effects might contribute to its overall beneficial properties. Here, we investigated the effects of a Sinupret® drug mixture (SIN) as well as of the novel Sinupret® dry extract (SIN DE) with the latter containing higher concentrations of active ingredients, in an in vivo model of acute inflammation, the carrageenan-induced pleurisy in rats. Both SIN and SIN DE were administered to rats orally at doses of 100mg/kg (low dose) and 500mg/kg (high dose) 1h prior to intrapleural injection of carrageenan. Although both SIN and SIN DE significantly reduced the exudate volume and leukocyte numbers in the pleural exudate at the high and the low dose 4h after carrageenan injection, the novel SIN DE was more efficient than SIN at the low dose, implying higher efficiency. In parallel, the novel dry extract SIN DE, but not SIN, at 500mg/kg significantly lowered the levels of prostaglandin (PG)E(2) in the exudates and reduced the amounts of cyclooxygenase (COX)-2 protein in the lungs. Together, SIN and SIN DE exert significant oral anti-inflammatory effects, which rationalize their therapeutic use in the management of sinusitis and other viral/microbial nasal infections that are associated with inflammation. Moreover, our results suggest that based on the higher efficiency and the accompanied reduction of COX-2 expression and PGE(2) formation, the novel dry extract SIN DE might be superior over the former SIN drug mixture.

Anti-inflammation effects of corn silk in a rat model of carrageenin-induced pleurisy.

Pleurisy is an inflammation of the pleural layers that surround the lungs. Despite much research into inflammatory diseases, no drugs with favorable safety profiles are available yet for their treatment. Corn silk has been used in many parts of the world for the treatment of edema, cystitis, gout, kidney stones nephritis, and prostitutes. However, no scientific reports on the anti-inflammatory effects of corn silk were so far available. To test the anti-inflammatory efficacy of corn silk extract (CSEX) in a rat model of carrageenin (Cg)-induced pleurisy, exudate formation, and cellular infiltration, tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), vascular endothelial growth factor alpha (VEGF-α), interleukin-17 (IL-17), C3 and C4 complement protein levels, adhesion molecule (ICAM-1) and inducible nitric oxide synthase (iNOS) levels, nuclear factor kappa B (NF-κB) activation, and total antioxidant activity were studied, respectively. Pretreatment with CSEX reduced Cg-induced pleurisy exudate, number of leukocytes, oxidative stress, C3 protein level, and O (2)(-) levels at the inflammatory site. Pretreatment with CSEX also inhibited TNF-α, IL-1ß, VEGF-α, and IL-17A and blocked inflammation-related events (ICAM-1 and iNOS) by activation of NF-κB. Supplementation with CSEX may be a promising treatment for inflammatory diseases that involve oxidative stress.

Carvacrol attenuates mechanical hypernociception and inflammatory response.

Carvacrol is a phenolic monoterpene present in the essential oil of the family Lamiaceae, as in the genera Origanum and Thymus. We previously reported that carvacrol is effective as an analgesic compound in various nociceptive models, probably by inhibition of peripheral mediators that could be related with its strong antioxidant effect observed in vitro. In this study, the anti-hypernociceptive activity of carvacrol was tested in mice through models of mechanical hypernociception induced by carrageenan, and the involvement of important mediators of its signaling cascade, as tumor necrosis factor-alpha (TNF-α), prostaglandin E(2) (PGE(2)), and dopamine, were assessed. We also investigated the anti-inflammatory effect of carvacrol on the model of carrageenan-induced pleurisy and mouse paw edema, and the lipopolysaccharide (LPS)-induced nitrite production in murine macrophages was observed. Systemic pretreatment with carvacrol (50 or 100 mg/kg; i.p.) inhibited the development of mechanical hypernociception and edema induced by carrageenan and TNF-α; however, no effect was observed on hypernociception induced by PGE(2) and dopamine. Besides this, carvacrol significantly decreased TNF-α levels in pleural lavage and suppressed the recruitment of leukocytes without altering the morphological profile of these cells. Carvacrol (1, 10, and 100 µg/mL) also significantly reduced (p < 0.001) the LPS-induced nitrite production in vitro and did not produce citotoxicity in the murine peritoneal macrophages in vitro. The spontaneous locomotor activity of mice was not affected by carvacrol. This study adds information about the beneficial effects of carvacrol on mechanical hypernociception and inflammation. It also indicates that this monoterpene might be potentially interesting in the development of novel tools for management and/or treatment of painful conditions, including those related to inflammatory and prooxidant states.

On the inhibition of 5-lipoxygenase product formation by tryptanthrin: mechanistic studies and efficacy in vivo.

BACKGROUND AND PURPOSE: Leukotrienes (LTs) are pro-inflammatory mediators produced by 5-lipoxygenase (5-LO). Currently available 5-LO inhibitors either lack efficacy or are toxic and novel approaches are required to establish a successful anti-LT therapy. Here we provide a detailed evaluation of the effectiveness of the plant-derived alkaloid tryptanthrin as an inhibitor of LT biosynthesis. EXPERIMENTAL APPROACH: We analysed LT formation and performed mechanistic studies in human neutrophils stimulated with pathophysiologically relevant stimuli (LPS and formyl peptide), as well as in cell-free assays (neutrophil homogenates or recombinant human 5-LO) and in human whole blood. The in vivo effectiveness of tryptanthrin was evaluated in the rat model of carrageenan-induced pleurisy. KEY RESULTS: Tryptanthrin potently reduced LT-formation in human neutrophils (IC(50) = 0.6µM). However, tryptanthrin is not a redox-active compound and did not directly interfere with 5-LO activity in cell-free assays. Similarly, tryptanthrin did not inhibit the release of arachidonic acid, the activation of MAPKs, or the increase in [Ca(2+) ](i) , but it modified the subcellular localization of 5-LO. Moreover, tryptanthrin potently suppressed LT formation in human whole blood (IC(50) = 10µM) and reduced LTB(4) levels in the rat pleurisy model after a single oral dose of 10mg·kg(-1) . CONCLUSIONS AND IMPLICATIONS: Our data reveal that tryptanthrin is a potent natural inhibitor of cellular LT biosynthesis with proven efficacy in whole blood and is effective in vivo after oral administration. Its unique pharmacological profile supports further analysis to exploit its pharmacological potential.